Reading difficulties may have multiple causes. Effective approaches to reading intervention need to target the specific causes for individual readers. The Early Reading Intervention Knowledge program comprises three intervention pathways: a phonological-phonemic pathway, a phonic-orthographic pathway, and an oral language pathway. This study examines the effectiveness of each pathway for 902 underachieving students in their second to fifth years of primary education. The students differed in their reading profiles. The interventions were implemented in a regular school context. Intervention in the three pathways improved reading accuracy and comprehension for both the younger (Years 2 and 3) and older (Years 4 and 5) age groups. The pattern in accuracy gains across the three pathways was similar for each group, with the older students making smaller gains. Reading profiles influenced the rate or amount of gain. For comprehension, the phonological and oral language pathways yielded higher gains for both age groups than the orthographic pathway. The most at-risk students showed the highest gains. The implications for intervention are discussed.